The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia

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dc.citation.issue2
dc.citation.volume22
dc.contributor.authorFernandes, Gustavo W. [UNIFESP]
dc.contributor.authorBocco, Barbara M. L. C. [UNIFESP]
dc.contributor.authorFonseca, Tatiana L.
dc.contributor.authorMcAninch, Elizabeth A.
dc.contributor.authorJo, Sungro
dc.contributor.authorLartey, Lattoya J.
dc.contributor.authorO-Sullivan, InSug
dc.contributor.authorUnterman, Terry G.
dc.contributor.authorPreite, Nailliw Z.
dc.contributor.authorVoigt, Robin M.
dc.contributor.authorForsyth, Christopher B.
dc.contributor.authorKeshavarzian, Ali
dc.contributor.authorSinko, Richard
dc.contributor.authorGoldfine, Allison B.
dc.contributor.authorPatti, Mary E.
dc.contributor.authorRibeiro, Miriam O.
dc.contributor.authorGereben, Balazs
dc.contributor.authorBianco, Antonio C.
dc.coverageCambridge
dc.date.accessioned2020-07-08T13:09:53Z
dc.date.available2020-07-08T13:09:53Z
dc.date.issued2018
dc.description.abstractLiver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in resistance to both diet-induced obesity and liver steatosis in mice. Here, we report that this is explained by an similar to 60% reduction in liver zinc-finger protein-125 (Zfp125) expression. Zfp125 is a Foxo1-inducible transcriptional repressor that causes lipid accumulation in the AML12 mouse hepatic cell line and liver steatosis in mice by reducing liver secretion of triglycerides and hepatocyte efflux of cholesterol. Zfp125 acts by repressing 18 genes involved in lipoprotein structure, lipid binding, and transport. The ApoE promoter contains a functional Zfp125-binding element that is also present in 17 other lipid-related genes repressed by Zfp125. While liver-specific knockdown of Zfp125 causes an "Alb-D2KO-like'' metabolic phenotype, liver-specific normalization of Zfp125 expression in Alb-D2KO mice rescues the phenotype, restoring normal susceptibility to diet-induced obesity, liver steatosis, and hypercholesterolemia.en
dc.description.affiliationRush Univ, Med Ctr, Div Endocrinol & Metab, Chicago, IL 60612 USA
dc.description.affiliationUniv Fed Sao Paulo, Program Translat Med, Sao Paulo, Brazil
dc.description.affiliationUniv Illinois, Coll Med, Dept Med, Sect Endocrinol Diabet & Metab, Chicago, IL USA
dc.description.affiliationRush Univ, Div Digest Dis & Nutr, Med Ctr, Chicago, IL 60612 USA
dc.description.affiliationHarvard Med Sch, Joslin Diabet Ctr, Boston, MA USA
dc.description.affiliationUniv Prebiteriana Mackenzie, Ctr Biol Sci & Hlth, Dev Disorders Program, Sao Paulo, Brazil
dc.description.affiliationHungarian Acad Sci, Inst Expt Med, Dept Endocrine Neurobiol, Budapest, Hungary
dc.description.affiliationUnifespUniv Fed Sao Paulo, Program Translat Med, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNIDDK
dc.description.sponsorshipEU
dc.description.sponsorshipHungarian Brain Research Program
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipCoordenadoria de Apoio a Pesquisa (CAPES), Brazil
dc.description.sponsorshipIDNIDDK: DK65055, R01DK106193, P30DK036836
dc.description.sponsorshipIDEU: 666869
dc.description.sponsorshipIDHungarian Brain Research Program: KTIA_13_NAP_A_I/4
dc.description.sponsorshipIDFAPESP: 2011/21847-6
dc.format.extent523-534
dc.identifierhttp://dx.doi.org/10.1016/j.celrep.2017.12.053
dc.identifier.citationCell Reports. Cambridge, v. 22, n. 2, p. 523-534, 2018.
dc.identifier.doi10.1016/j.celrep.2017.12.053
dc.identifier.fileWOS000419587900018.pdf
dc.identifier.issn2211-1247
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54269
dc.identifier.wosWOS:000419587900018
dc.language.isoeng
dc.publisherCell Press
dc.relation.ispartofCell Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleThe Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemiaen
dc.typeinfo:eu-repo/semantics/article
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